Patients with sleep disordered breathing (SDB) have variable contributions from upper airway obstruction and abnormal control of breathing. The latter is best demonstrated by Cheyne-Stokes respiration (e.g., in congestive cardiac failure), but a lesser degree of periodic breathing is a common finding in clinical practice. See reference [1] below. The greater the contribution from abnormal control, the less effective are therapies based on air pressure support of the upper airway, such as continuous or bilevel positive airway pressure (xPAP). See reference [2] below. Additional oxygen is a commonly used therapeutic adjunct, even if hypoxia is not severe, but does not fully treat periodic breathing. See reference [3] below.
It has been known for over fifty years that disordered carbon dioxide homeostasis in the blood is fundamental to the development of periodic breathing patterns. It has also been known that increasing the concentration of CO2 in inspired air by 2-6% has a profound and immediate stabilizing effect on respiration during sleep (see reference [4] below). Supplemental CO2 stabilizes breathing by damping the variations in CO2 concentration in the blood caused by hyperventilation and hypoventilation, and by increasing the average partial pressure of CO2 in the blood. Nevertheless, the practical difficulty of using CO2, along with the development of xPAP technology, has resulted in little clinical interest in developing methods of improving sleep-breathing quality through its use. The use of xPAP technology together with carbon dioxide presents even more difficult practical problems.
Many SDB patients who are treated with xPAP have residual symptoms. The resulting sleep fragmentation is considered clinically important. See reference [5] below. While xPAP therapy is often highly effective in treating non-complex obstructive SDB, patients with more complex disease usually fail xPAP therapy. Such patients typically have evidence of overt or subtle periodic breathing and may have a mix of obstructive apneas, hypopneas and central apneas. Often, these patients will be more unstable during non-REM versus REM sleep. Even with the addition of oxygen to PAP these patients as a group are very difficult to treat.
There are three major populations with difficult-to-control SDB within the context of periodic breathing: 1) Patients with congestive cardiac failure or renal failure and overt Cheyne-Stokes respiration; 2) Patients with overt Cheyne-Stokes respiration but no heart failure or renal failure; and 3) Patients with more subtle but important degrees of periodic breathing (no pure Cheyne-Stokes respiration), with or without heart/renal failure. The majority of patients with difficult-to-control SDB currently seen in sleep clinics may fall into this latter category.
Each of the references below is incorporated herein by reference:
1. Thalhofer S., Dorow P. Sleep-Breathing Disorders and Heart Failure. Sleep Breath 2000;4:103-112.
2. Teschler H., Dohring J., Wang Y. M., Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med 2001;164:614-619.
3. Krachman S. L., D=Alonzo G. E., Berger T. J., Eisen H. J. Comparison of oxygen therapy with nasal continuous positive airway pressure on Cheyne-Stokes respiration during sleep in congestive heart failure. Chest 1999;116:1550-1557.
4. Lorenzi-Filho G., Rankin F., Bies I., Douglas, Bradley T. Effects of inhaled carbon dioxide and oxygen on cheyne-stokes respiration in patients with heart failure. Am J Respir Crit Care Med 1999;159:1490-1498.
5. Pack A. I., Black J. E., Schwartz J. R., Matheson J. K. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 2001;164:1675-1681.